Any and all applications for which a foreign or domestic priority claim is identified in the Application Data Sheet as filed with the present application are hereby incorporated by reference under 37 CFR 1.57.
Field of the Invention
The present invention relates to a substance delivery carrier targeted at extracellular matrix-producing cells in the lung, and a therapeutic agent for pulmonary fibrosis and a method for treating pulmonary fibrosis utilizing the carrier.
Description of the Related Art
Pulmonary fibrosis is a disease characterized by diffuse fibroplasia of the alveolar walls, and its main symptoms include dry cough and dyspnea on exertion. In a restricted sense, it refers to end-stage disease states of interstitial pneumonia; while in a broad sense, it means a co-existing state of pulmonary fibrosis in a restricted sense with interstitial pneumonia. Any interstitial pneumonia can cause pulmonary fibrosis. Interstitial pneumonia is a generic term for the diseases that induce inflammation in interstices of the lung (including alveolar septum in a restricted sense, and intralobular interstice and the vicinity of pleural membrane in a broad sense); it includes those induced by a specific cause such as infection, collagen disease, radiation, drug, and dust, and those without any known cause, i.e., idiopathic interstitial pneumonia. Idiopathic interstitial pneumonia is further classified as follows based on the findings of video-assisted thoracoscopic surgery (VATS) and high-resolution computer tomography (HRCT): idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), lymphoid interstitial pneumonia (LIP), etc. Many of the interstitial pneumonia with specified causes are cured by elimination of the causes and administration of anti-inflammatory agents such as steroid drugs. However, regarding idiopathic interstitial pneumonia, there is no radical treatment method to date, and only treatments such as administration of steroid drugs, azathioprine and cyclophosphamide during exacerbation of symptoms, and oxygen therapy during development of hypoxemia are performed; accordingly, there are many dead cases in which idiopathic interstitial pneumonia progresses into pulmonary fibrosis. Therefore, the average survival period after establishment of diagnosis of idiopathic interstitial pneumonia is as short as 2.5-5 years, and this disease is designated as one of the specific diseases in Japan.
Under such circumstances, much research effort has been made to the development of therapeutic agents for pulmonary fibrosis. As a result, pharmaceutical agents such as colchicine, D-penicillamine, pirfenidone (5-methyl-1-phenyl-2-[1H]-pyridone), interferon-β1a, relaxin, lovastatin, beractant, N-acetylcysteine, keratinocyte growth factor, captopril (Non Patent Literature 1), hepatocyte growth factor (Patent Literature 1), Rho-kinase inhibitor (Patent Literature 2), thrombomodulin-like protein (Patent Literature 3), bilirubin (Patent Literature 4), PPARγ (peroxisome proliferator-activated receptor gamma) activator (Patent Literature 5), imatinib (Patent Literature 6), interferon-γ (Patent Literature 7) have been reported to show some effectiveness in animal models of pulmonary fibrosis or clinical trials. However, none of these agents is not yet satisfactory, and further development of the therapeutic agents for pulmonary fibrosis has been awaited.